EVIDENCE FOR HORMONE-SENSITIVE LIPASE MESSENGER-RNA EXPRESSION IN HUMAN MONOCYTE MACROPHAGES/

The role of hormone-sensitive lipase (HSL) in the hydrolysis of adipos e tissue triacylglycerol to provide free fatty acids for energy requir ements has been well established. However, the role of HSL in other ti ssues, including macrophages, is not well understood. The demonstratio n that HSL is capable of hydrolyzing cholesteryl esters at approximate ly the same rate as triacylglycerol raised the possibility that HSL ac tivity in macrophages may influence the accumulation of cholesteryl es ters in foam cells of atherosclerotic lesions. We and others have prev iously demonstrated that HSL mRNA is expressed in murine peritoneal ma crophages and macrophage cell lines; however, it was previously report ed chat HSL mRNA is absent in human monocyte-derived macrophages, sugg esting that a species difference may exist. To clarify this point, we have further examined the issue of HSL mRNA expression in human macrop hages. In the current study. we demonstrate that HSL mRNA is detectabl e in human monocyte derived macrophages and in the THP-1 human monocyt e cell line using reverse transcription coupled to polymerase chain re action (RT-PCR). Specific amplification of cDNA derived from mRNA was ensured by using primers that span an intron within the human HSL gene , and the identity of PCR products as HSL was confirmed by hybridizati on to HSL cDNA and by DNA sequencing. Using a semiquantitative PCR ass ay, we establish that HSL mRNA levels in monocyte/macrophages are appr oximately 1/40 the levels in human adipose tissue. These results indic ate that further studies addressing the role of HSL in macrophage meta bolism and its potential role in development of foam cells in human at herosclerotic lesions are warranted.